First Insight into the Seroepidemiology of Hepatitis E Virus (HEV) in Dogs, Cats, Horses, Cattle, Sheep, and Goats from Bulgaria.

In recent years, hepatitis E virus (HEV) infection has been found to be widespread among different animal species worldwide. In Bulgaria, high HEV seropositivity was found among pigs (60.3%), wild boars (40.8%), and East Balkan swine (82.5%). The aim of the present study was to establish the seroprevalence of HEV among dogs, cats, horses, cattle, sheep, and goats in Bulgaria. In total, 720 serum samples from six animal species were randomly collected: dogs-90 samples; cats-90; horses-180; cattle-180; sheep-90; and goats-90. The serum samples were collected from seven districts of the country: Burgas, Kardzhali, Pazardzhik, Plovdiv, Sliven, Smolyan, and Stara Zagora. The animal serum samples were tested for HEV antibodies using the commercial Wantai HEV-Ab ELISA kit (Beijing, China). The overall HEV seroprevalence among different animal species from Bulgaria was as follows: dogs-21.1%; cats-17.7%; horses-8.3%; cattle-7.7%; sheep-32.2%; and goats-24.4%. We found the lowest overall HEV seropositivity in Plovdiv district (6.2%; 4/64; p = 0.203) and Smolyan district (8.8%; 4/45; p = 0.129), vs. the highest in Pazardzhik district (21.6%; 29/134; p = 0.024) and Burgas district (28.8%; 26/90; p = 0.062). To the best of our knowledge, this is the first serological evidence of HEV infection in dogs, cats, horses, cattle, sheep, and goats from Bulgaria. We found high HEV seropositivity in small ruminants (sheep and goats), moderate seropositivity in pets (dogs and cats), and a low level of seropositivity in large animals (horses and cattle). Previous Bulgarian studies and the results of this research show that HEV infection is widespread among animals in our country. In this regard, the Bulgarian health authorities must carry out increased surveillance and control of HEV infection among animals in Bulgaria.

Comparative Analysis on Clinical Characteristics Among Patients with Acute Hepatitis A Virus (HAV) and Patients with Acute Hepatitis E Virus (HEV): A Single-Center Retrospective Study from Bulgaria.

Introduction: The acute viral hepatitis was one of the most common conditions in daily clinical practice varying in different parts of the world. The aim of the present study was to perform a comparative analysis on clinical characteristics among patients with acute hepatitis A virus (HAV) infection and patients with acute hepatitis E virus (HEV) infection admitted to the Military Medical Academy (MMA), Sofia, Bulgaria. Methods: A retrospective study was performed at MMA, between 1 January 2016 and 31 December 2021. The etiological diagnosis was confirmed by enzyme-linked immunosorbent assay (ELISA) HAV/HEV IgM serology assays. Results: The current survey included 231 patients with mean age 45.11 ± 16.08 years (95% confidence interval: 43.04-47.19). According to the case definition, inclusion and exclusion criteria, persons were divided into two groups: patients with acute HAV infection (68.4%; 158/231) and patients with acute HEV infection (31.6%; 73/231). Males with HEV had 3.091 times the odds of comorbidity "hypertension" than males with HAV (p = 0.032). There were almost equal odds of increased ALT (odds ratio = 0.999; p = 0.003) in men with HEV and men with HAV. Females with HEV had 5.161 times the odds of comorbidity "hypertension" compared with females with HAV (p = 0.049). We found almost equal odds for elevated ALT in women with HEV and women with HAV (OR = 0.999; p = 0.025). In the non-elderly group (<60-year-old), HEV individuals had 4.544 and 10.560 times the odds of comorbidities "hypertension" and "cardiovascular diseases" compared with HAV patients (p < 0.05). We found almost equal odds for elevated ALT in HEV patients and HAV participants (OR = 0.998; p = 0.002). Conclusion: The results from the current study may support the physicians daily care for patients with acute HAV and acute HEV.

Analysis of Bacterial Biofilm Formation and MUC5AC and MUC5B Expression in Chronic Rhinosinusitis Patients.

Chronic rhinosinusitis (CRS) is a condition affecting as much as 16% of the adult population in developed countries with many factors attributed to its development, including the more recently proposed role of bacterial biofilm infections. Plenty of research has been conducted on biofilms in CRS and the causes behind the development of such an infection in the nasal cavity and sinuses. One such probable cause is the production of mucin glycoproteins by the mucosa of the nasal cavity. To investigate the possible link between biofilm formation and mucin expression levels and their relationship with CRS etiology, we examined samples from 85 patients by means of spinning disk confocal microscopy (SDCM) to establish their biofilm status and quantitative reverse transcription polymerase chain reaction (qRT-PCR) to determine MUC5AC and MUC5B expression levels. We observed a significantly higher prevalence of bacterial biofilms in the CRS patient group compared to the control group. In addition, we detected higher expression levels of MUC5B but not MUC5AC in the CRS group, which suggested a possible role for MUC5B in CRS development. Finally, we found no direct relationship between biofilm presence and mucin expression levels, thereby showing a multifaceted connection between these two major factors implicated in CRS etiology.

Durability of humoral and cell-mediated immune response after SARS-CoV-2 mRNA vaccine administration.

Vaccination against the SARS-Cov-2 virus is an effective way to protect against the disease and the severe course of COVID-19. Forty-nine fully vaccinated with mRNA vaccines (BNT162b2 or mRNA-1273) SARS-CoV-2 infection-naïve volunteers aged 33-89 were enrolled in the study. Evaluation of the cellular and humoral immune response was performed within 1 to 3 months (T1) and 6-9 months (T2) after the second injection, and within 2-3 months (T3) after a booster dose. Additionally, a comparative analysis of the specific immune status was made between two age groups-below 60 (n = 22) and over 60 (n = 27) years. SARS-CoV-2-specific T-cell response was evaluated by IFN-γ-producing spot forming cells (SFCs) using a standardized ELISPOT assay. Virus neutralizing antibodies (VNA) against SARS-CoV-2 were measured by a blocking ELISA test and spike protein specific IgG (S-IgG) and IgA (S-IgA) antibodies-by semiquantitative ELISA. IFN-γ-producing SFCs, S-IgG, S-IgA and VNA significantly decreased 6-9 months after the second dose. After the third injection S-IgG and S-IgA markedly increased compared to T2 and reached the levels at T1. Of note, the highest values of VNA were observed at T3. No differences in the tested immune parameters were found between the two age groups. Data obtained showed that for a long period-6-9 months after a full course of immunization with mRNA vaccine, immune reactivity is present, but both cellular and humoral immune responses gradually decrease. The administration of a third dose mainly restores the specific humoral immune response against the SARS-CoV-2 virus.

Dexamethasone Coanalgesic Administration in Steroid Naïve and Steroid Non-Naïve Patients for the Prevention of Pain Flares after Palliative Radiotherapy for Bone Metastases.

Objective: Dexamethasone could be an effective prophylactic agent for the prevention of pain flares after palliative radiotherapy (RT) for uncomplicated bone metastases. To date, there are no data on its prophylactic coanalgesic (opioid-sparing) effect after RT in patients with complicated bone metastases compared to uncomplicated ones, which is the aim of our study. Methods: Twenty-nine American Society of Anaesthesiologists (ASA) III-IV patients, aged ≥18, treated with single-fraction 8 Gy/1 or multi-fraction 20 Gy/5 RT for painful uncomplicated bone metastases (steroid naïve patients, n = 14) or complicated ones (steroid non-naïve patients, n = 15), were examined retrospectively. All patients received parenteral dexamethasone (4 mg or 8 mg daily, 1 hour before RT, followed by the same dose for the next 4 days) along with their background and breakthrough pain opioid intake (morphine equivalents) during their 5-day in-hospital stay. Pain severity (numeric rating scale) and analgesic consumption were recorded at admission, daily during the hospital stay, and for 10 days following treatment. Binary logistic regression was used to determine predictive factors for pain flare occurrence. Results: A higher ASA score is the only determinant positively influencing opioid consumption (P = 0.018) and pain flare as well (OR = 15.00; 95% CI: 2, 24-100, 48; P = 0.005). Lower dose 4 mg dexamethasone was revealed as a moderate analgesic agent in steroid naïve patients with no side effects, whereas in steroid non-naïve patients the predominantly higher dose 8 mg dexamethasone had minimal impact on pain flares prevention at the expense of more pronounced immunosuppression (P = 0.039). Conclusions: Irrespective of the supporting evidence of dexamethasone potential for prevention of RT-induced pain flare, our data failed to reveal its efficacy in the real practice world (a case mix of uncomplicated and complicated bone metastases). Further dose-effect bigger studies are needed, identifying optimal doses of dexamethasone intake and its optimal duration in high-risk patients.

Serological Searching for Hepatitis E Virus Infection Among Pig Liver Transudate from Bulgaria: An Alternative Method for Seroepidemiological Survey.

Background: The aim of this research was to perform a seroepidemiological survey of hepatitis E virus (HEV) by an alternative method-serological establishment of the virus from pig liver transudate. This is the first such research in Bulgaria. Moreover, no studies have been conducted on HEV in pig liver in our country. Materials and Methods: A total of 90 liver samples from healthy pigs were collected from slaughterhouses in three parts of the country (Sofia, Lovech, and Stara Zagora districts). An equal number of samples (n = 30) were obtained from each district. Results: The overall HEV seropositivity was 67.7% of all 90 tested pig liver transudate samples; in Sofia district 20.0%, in Lovech district 90.0%, and in Stara Zagora district 93.3%. Conclusion: These data are similar to our previous serological studies for HEV in serum samples from industrial pigs, wild boars, and East Balkan swine. In this regard, testing the liver transudate could be a fine alternative method for seroepidemiological survey on HEV in swine.

Students' Attitudes toward COVID-19 Vaccination: An Inter-University Study from Bulgaria.

In Bulgaria, vaccination coverage against the SARS-CoV-2 virus is low. The reasons for this fact are many and varied. The aim of the present study was to establish what the attitudes towards the COVID-19 vaccination process are among students from various specialties from several Bulgarian universities. In this research, 600 students participated, divided into two groups: Doctor of Medicine (MD) students (n = 300) and non-MD students, i.e., students of specialties, such as mathematics, engineering, finance and economics, law, human sciences, etc. (n = 300). Each respondent completed a questionnaire which was divided into three parts with closed questions. The mean age of all students was 21.19 ± 1.87 years (95% CI: 20.48−21.90). The female sex dominated among the analyzed participants (sex ratio: female/male = 1/0.85). Nearly 62% (371/600) of individuals declared that they have been COVID-19 vaccinated with at least one dose (p < 0.001). Overall, 33% of the participants sought information on vaccines from video sharing platforms and 36.0% (216/600) from social media platforms. From the conducted multivariable logistic regression the odds of vaccination against COVID-19 were 6.225 times higher in individuals with a positive attitude towards these vaccines than in people with a negative attitude towards them (p < 0.001). We have found that those students who trust the international health organizations had an OR of 2.365 (p = 0.004) to be SARS-CoV-2 vaccinated. We estimated that the odds of vaccination against SARS-CoV-2 among children were 4.794 times higher in parents (students) who had been vaccinated than in non-vaccinated parents (students) (p < 0.001). Our results could support the national public health organizations, the national educational/scientific systems, and the management of Bulgarian universities in making future decisions about the field of COVID-19 control and prevention.

Hydroxychloroquine (HCQ) Treatment for Hospitalized Patients with COVID- 19.

OBJECTIVE: Studies have indicated that hydroxychloroquine (HCQ) exerts antiviral effects against SARS-CoV-2 in vitro. However, trials regarding its effects on patients are very controversial. This study aims to evaluate the efficacy of (HCQ) in the treatment of hospitalized patients with COVID-19. METHODS: We prospectively enrolled 260 patients hospitalized for COVID-19 in Heart and Brain Center of Excellence- Pleven, Bulgaria, for the period from November 6 to December 28, 2020. This study is not randomized, which we compensated for with Propensity Score Matching. Patients in the HCQ group were given HCQ 200 mg 3 times a day (600mg daily) for the duration of their hospitalization plus conventional treatment, while those in the control group were given conventional treatment only. The primary endpoints were transferred to the intensive care unit, needed for mechanical ventilation, and in-hospital death. RESULTS: Of the 260 COVID-19 patients, 178 (68.5%) were male and the mean age was of 63.78 ± 12.45 years, with the most prevalent comorbidity hypertension (68.5%). We had two subgroups: treated with HCQ and conventional treatment (128 patients) and treated with conventional treatment only (132 patients). In the primary analysis, patients in the HCQ group presented with fewer comorbidities and were younger than the group without HCQ. Patients treated with HCQ demonstrated a significant benefit in the primary endpoints compared to those without HCQ, namely, transferred to ICU - 20 (20,8%) vs. 41 (36.9%), p=0.011, need for mechanical ventilation 13 (13.4%) vs. 33 (28.2%), p=0.009 and in-hospital death 14 (10.9%) vs. 35 (26.5%), p=0,001, respectively. We repeated this analysis with PSM, where 70 matched pairs were identified. Regarding the primary endpoints, we found again a statistically significant difference between the groups. Comparing transferring to ICU, better outcomes were presented in the HCQ group: 8 (17.4%) vs. 27 (44.3%), with p= 0.003. Besides, a smaller proportion of the patients needed mechanical ventilation: 6 (12.8%), compared to the control group, 23 (35.4%), p= 0.007. Notably, patients from the HCQ group died during hospitalization: 8 (11.4%) in comparison with 19 (27.1%) from the control group, p= 0.018. CONCLUSION: Patients treated with HCQ demonstrated a significant benefit in the primary endpoints in our study, namely, transfer to the intensive care unit, need for mechanical ventilation, and in-hospital death. HCQ improves prognosis in hospitalized patients with COVID-19.

Serological evidence of hepatitis E virus infection in pigs from Northern Bulgaria.

The purpose of the present study was to investigate pigs in Northern Bulgaria for serological evidence of hepatitis E virus (HEV). Sera from 225 individuals from three industrial farms were tested for anti­HEV IgG antibodies. The overall HEV seroprevalence was 36% (81/225); weaners 6.8% (5/74); fattening pigs 38.7% (29/75) and in sows 61.8% (47/76). Compared to weaners, HEV positivity was higher in fattening pigs and sows: OR = 8.70 (95% CI: 3.14­24.12) and OR = 22.37 (95% CI: 8.07­61.96), respectively. These data confirm that HEV is endemic in pigs throughout Bulgaria, and can be a Public Health problem due to the transmission of HЕV to humans through the consumption of pork meat and pork products.

Seroprevalence of Hepatitis E Virus Infection among Blood Donors in Bulgaria.

Hepatitis E virus (HEV) infection is widespread among domestic pigs, industrial swine, and wild boars in Bulgaria. The aim of the current research was to present the HEV seroprevalence among blood donors in Bulgaria. In the present study, 555 blood donors (479 males and 76 females) were enrolled from five districts in the country (Shumen, Pleven, Stara Zagora, Plovdiv, and Sofia districts). All blood samples were tested for anti-HEV IgG using the recomWell HEV IgG ELISA test (Mikrogen GmbH, Neuried, Germany). Each participating donor completed a short, structured, and specific questionnaire to document data on the current study. Anti-HEV IgG positive results were detected in 144 (25.9%) blood donors, including 129 (26.9%) males and 15 (19.7%) females. The established HEV seropositivity was 28.8% (23/80) in Shumen district, 23.2% (22/95) in Pleven district, 27.1% (38/140) in Stara Zagora district, 27.5% (44/160) in Plovdiv district, and 21.3% (17/80) in Sofia district. A high HEV seroprevalence was found for persons who declared that they were general hunters (48.7%; 19/39; p = 0.001) and hunters of wild boars (51.6%; 16/31; p = 0.001). We present the first seroprevalence rates of HEV infection in blood donors from Bulgaria. The results of our research showed high HEV seropositivity among blood donors.

Seroprevalence of Hepatitis E Virus Infection Among Wild Boars in Western Bulgaria.

Scientific evidence indicates that hepatitis E virus (HEV) infection is a zoonotic disease. Domestic pigs and wild boars are the main animal reservoir for HEV worldwide. The aim of this study was to analyze the seroprevalence of HEV infection among wild boars in western Bulgaria. Serum samples from 240 wild boars from two regions of the country (northwestern and southwestern) were tested for anti-HEV Immunoglobulin G (IgG) antibodies. The overall HEV seroprevalence was 40.8% (98/240); northwestern region 40.0% (48/120); southwestern region 41.7% (50/120). HEV seropositivity in the southwestern region was higher than in the northwestern region: odds ratio = 1.071 (95% confidence interval: 0.640-1.793). This research provided the first seroprevalence study to HEV in wild boars from western Bulgaria.

High Seroprevalence of Hepatitis E Virus Infection Among East Balkan Swine (Sus scrofa) in Bulgaria: Preliminary Results.

The East Balkan swine (Sus scrofa) is the only aboriginal pig breed in Bulgaria, and it is indigenous to the eastern part of the country. The aim of the present study was to investigate East Balkan swine (EBS) in Bulgaria for serological evidence of hepatitis E virus (HEV). Sera from 171 swine from two parts of the country (northeastern and southeastern) were tested for anti-HEV IgG antibodies. The overall HEV seroprevalence was 82.5% (141/171), and for weaners it was 77.2% (44/57), for fattening pigs 79.0% (45/57), and for adults 91.2% (52/57). HEV positivity was higher in fattening pigs and adults compared to weaners: OR = 1.108 (95% CI: 0.456-2.692) and OR = 3.073 (95% CI: 1.016-9.294), respectively. This study provides the first evidence of exposure to HEV in EBS from Bulgaria.

Clinical Characteristics of Hospitalized Patients with COVID-19 in Sofia, Bulgaria.

Introduction: SARS-CoV-2 infection is spreading around the world, including countries from Southeastern Europe. The purpose of the study was to present the clinical manifestations of COVID-19 patients admitted to the Military Medical Academy, Sofia, Bulgaria. Materials and Methods: A retrospective study was conducted for a period of 3 months from March 2020 to June 2020 on this infection in our hospital. All participants were laboratory confirmed cases of COVID-19. RT-PCR was performed for etiological diagnosis. The hospitalized patients were divided into two groups on admission, that is, nonsevere and severe. Results: One hundred thirty-eight COVID-19 patients were hospitalized and analyzed during the study period. The mean age was 52.9 years. Male was the dominant sex (sex ratio: male/female = 1/0.6). The leading clinical signs were fever, fatigue, cough, and headache. On comparative analysis of both groups (nonsevere and severe) was measured significant elevation of white blood cells (odds ratio [OR] = 1.238; p value = 0.006), C-reactive protein (OR = 1.021; p < 0.001), creatinine (OR = 1.037; p < 0.001), aspartate aminotransferase (OR = 1.014; p = 0.040), lactate dehydrogenase (OR = 1.004; p < 0.001), ferritin (OR = 1.002; p < 0.001), fibrinogen (OR = 2.028; p < 0.001), and d-dimer (OR = 2.162; p = 0.002) in severe group than in nonsevere group. Interleukin 6 was tested in 17.4% of patients and high value was found-38.6 pg/mL (95% confidence interval: 16.5-60.7). Conclusion: The first Bulgarian retrospective study of COVID-19 hospitalized patients was presented. Older age, male sex, comorbidity, and signs of dyspnea and nausea were estimated as higher risk factors for severe form. Abnormality in inflammatory markers was associated with poor progression of the illness.

Seroprevalence Rates of Tick-Borne Pathogens in Cats from Southern Bulgaria.

The aim of the present study was to investigate the prevalence rates of the feline tick-borne pathogens (FTBPs)-Borrelia burgdorferi, Ehrlichia canis, and Anaplasma phagocytophilum in stray cats from Southern Bulgaria. Serum antibodies were used to estimate the prevalence of exposure to FTBPs from blood swabs. Of the 100 cat samples tested with in-clinic assay SNAP 4Dx Plus, the overall FTBP seroprevalence was 3% (3/100); with B. burgdorferi-1% (1/100) and E. canis-2% (2/100). This study provides the first evidence of exposure to B. burgdorferi and E. canis in cats from Bulgaria.

Obesity, Echocardiographic Changes and Framingham Risk Score in the Spectrum of Gout: A Cross-Sectional Study.

OBJECTIVES: This study aims to establish cardiovascular risk in obese and non-obese patients in stages of gout by using Framingham risk score (FRS) and transthoracic echocardiography. PATIENTS AND METHODS: This single-center cross-sectional study encompassed 201 patients (160 males, 41 females; mean age 56.9±13 years; range 20 to 89 years) including 52 asymptomatic hyperuricemia, 86 gouty arthritis without tophi, and 63 gouty tophi patients. Body Mass Index (BMI) and FRS were calculated. Left atrium (LA), interventricular septum, posterior wall (PW) of the left ventricle, fractional shortening (FS), mitral annular systolic velocity (S'), mitral annular early diastolic velocity (E') and transmitral to mitral annular early diastolic velocity ratio (E/E') were measured. Data were analyzed by Kolmogorov-Smirnov test, Shapiro-Wilk test, t-test, Mann-Whitney U test, analysis of variance test and multiple linear regression models. RESULTS: There was no significant difference in FRS, FS, S', E' and E/E' between obese and non-obese patients with asymptomatic hyperuricemia, gouty arthritis without tophi or gouty tophi. Obese patients in the three disease gradations had larger LA (p=0.007, p=0.004, p=0.039) and thicker PW (p=0.002, p=0.037, p=0.007). Increased BMI independently predicted the thickening of the PW in asymptomatic hyperuricemia (R2=0.319), gouty arthritis without tophi (R2=0.093) and gouty tophi (R2=0.068). CONCLUSION: Despite the lack of difference in FRS and functional systolic and diastolic parameters between obese and non-obese patients in the spectrum of gout, morphological heart changes were more pronounced in obese patients. In gouty tophi, it is possible that higher urate load together with chronic inflammation contribute for the alterations, as obesity worsens them.

Seroprevalence of Hepatitis E Virus Infection in Pigs from Southern Bulgaria.

Hepatitis E virus (HEV) has been isolated from humans and several animals' species. During the last years, the knowledge of HEV infection dramatically changed and enriched. The aim of this study was to estimate the seroprevalence of HEV in industrial pigs in different districts of Southern Bulgaria. Three hundred sixty swine serum samples were tested for anti-HEV IgG antibodies. The samples were collected from four industrial farms from three districts of Southern Bulgaria. HEV-specific antibodies in porcine serum were detected by enzyme-linked immunosorbent assay (PrioCHECK HEV Ab porcine). The overall HEV seroprevalence was 60.3%. The seropositivity varied widely depending on age groups and investigated farms. The overall prevalence in weaners was 25%, in fattening pigs 75.8%, and in group of sows was found the highest HEV positivity of 80%. The occurrence of HEV positivity in sows and fattening pigs presented odds ratio (OR) = 17.200 (95% confidence interval [CI]: 8.8-33.7) and OR = 11.342 (95% CI: 6.1-21.0), respectively, compared to weaners. The study indicated that HEV is widespread in industrial farms in Bulgaria and presented high seroprevalence in pigs. The results found that HEV seropositivity showed age dependency. The National Health Authorities should raise awareness of HEV and its zoonotic potential.

The Synergistic Effect of TNFA and IL10 Promoter Polymorphisms on Genetic Predisposition to Systemic Lupus Erythematosus.

AIMS: We investigated the individual and combined effect of functional TNFA -308G/A and IL10 -1082G/A single nucleotide polymorphisms (SNPs) and their genotypes on the susceptibility to systemic lupus erythematosus (SLE) in a Bulgarian population. MATERIALS AND METHODS: Genotyping for -1082A/G IL10 (rs1800896) and -308G/A TNFA (rs1800629) polymorphisms was performed for 154 SLE patients and 224 healthy controls. RESULTS: An association between SLE and the rs1800629 polymorphism was established under the allelic model (allele A vs. allele G; odds ratios [OR] = 2.317), the dominant model (GA+AA vs. GG; OR = 3.214), and the overdominant model (GA vs. AA+GG; OR = 3.494). There was no association between rs1800896 and SLE, although a tendency for genetic predisposition to SLE was observed for the IL10 -1082 GG genotype under the recessive genetic model (OR = 1.454). When analyzing the influence of the combined TNFA/IL10 genotypes on SLE occurrence, we found that the carriage of both high cytokine-producing genotypes of two SNPs (TNFA -308AA/GA and IL10 -1082GG) significantly increased the risk of developing SLE with OR of 9.026 (p = 0.006). CONCLUSION: Our findings suggest that the combinatorial complexity of TNFA and IL10 promoter polymorphisms impacts SLE susceptibility. Notably, we found that a TNFA promoter polymorphism is a leading risk factor for SLE susceptibility in a Bulgarian population, while the IL10 -1082 locus appears to act as a significant modifier.

Evaluation of cardiovascular risk in stages of gout by a complex multimodal ultrasonography.

The aim of our work was to assess ultrasound features of cardiovascular (CV) risk in stages of gout. Cross-sectional complex multimodal ultrasound study of 169 age-matched patients, with similar distribution of arterial hypertension, diabetes mellitus, obesity and chronic renal failure, was divided into four groups: 41 with asymptomatic hyperuricemia, 52 gout without tophi, 42 gouty tophi and 34 controls with osteoarthritis. Parameters independently associated with CV risk were measured: renal resistive index (RRI), left ventricular mass index (LVMi), mitral annulus early diastolic velocity (e'), intima-media thickness (IMT) and common carotid artery resistive index (CCARI). Multivariate analyses were performed to evaluate the impact of gout stages and CV risk factors on ultrasound alterations. Gouty tophi increased the risk of having IMT >0.90 mm with an OR 11.51 (95 % CI 2.32-57.21, p = 0.003), gout without tophi raised the risk with an OR 6.25 (95 % CI 1.37-28.44, p = 0.018), while asymptomatic hyperuricemia had no effect on IMT. The category of CCARI >0.70 was influenced by tophi with an OR 11.18 (95 % CI 2.61-47.83, p = 0.001) and by arterial hypertension with an OR 3.22 (95 % CI 1.11-9.36, p = 0.032). Neither asymptomatic hyperuricemia nor gout without tophi modified the development of abnormally high CCARI. Gout stages had no impact on LVMi, e' and RRI. Tophi are related to worsened ultrasonographic parameters evaluating target organs in gout, relative to earlier stages of the disease. They create a strong risk of carotid arteries' changes even beyond arterial hypertension.

Ultrasonographic measurement of carotid artery resistive index and diastolic function of the heart in gout patients.

The aim of the study was to establish the functional disorder in the blood circulation of gout patients with a method that shows early damage of the heart and vascular structures. A total of 117 patients were examined cross-sectionally by a complex multimodal ultrasonography and were divided into four groups: 37 healthy controls, 24 asymptomatic hyperuricemia, 36 gout without tophi and 20 gouty tophi. With pulsed Doppler, common carotid artery resistive index (CCARI) and parameters of the transmitral blood flow were determined: the ratio between maximal early and late flow velocities (E/A ratio) and deceleration time (DT). With tissue Doppler imaging, mitral annular peak velocity (Em) was obtained. In the examined ultrasonographic parameters between healthy controls and the three patient groups, there was a statistically significant difference (p < 0.001). Comparing asymptomatic hyperuricemia and gout without tophi, no significant difference in CCARI (p = 0.656), E/A ratio (p = 0.472), DT (p = 0.990) and Em (p = 0.488) was found. Gouty tophi in comparison with gout without tophi and asymptomatic hyperuricemia had significantly lower Em (mean ± SD 0.07 ± 0.02 vs 0.09 ± 0.03 vs 0.13 ± 0.17) and significantly higher CCARI (mean ± SD 0.74 ± 0.05 vs 0.70 ± 0.05 vs 0.69 ± 0.05). Further multiple logistic regression revealed that tophi increased subject's likelihood of having category of CCARI ≥ 0.7 with an OR = 10.91 (95 % CI 1.80-66.14, p = 0.009), while the category of Em < 0.08 m/s was influenced by renal insufficiency with an OR = 3.07 (95 % CI 1.17-8.02, p = 0.022). Gouty tophi are associated with progression of arteriosclerotic-type vessel changes. Worsening of diastolic dysfunction of the heart is independently associated with renal insufficiency. In terms of CV risk, tophi are an indicator of its increase.